Technical Abstract:
Malignant catarrhal fever (MCF) is a fulminant disease of certain susceptible ruminants caused by ovine herpesvirus 2 (OvHV-2). The characteristic lesions of MCF include lymphoproliferation, vasculitis and mucosal ulceration. The pathogenesis of these lesions is very poorly understood, but is most likely due to virally-induced dysregulation of cellular immune responses to host and/or viral antigens resulting in immune-mediated damage to vascular and epithelial tissues. However, the inability to culture OvHV-2 in vitro, and the lack of genetic information about OvHV-2, has precluded studies of viral gene expression in vivo. Recently two complete and annotated genome sequences of OvHV-2 have become available. Based on this information, we used PCR to detect viral mRNA for genes associated with both latent (ORF 73) and lytic infections (ORF 25 – capsid protein), as well as key immunomodulatory genes (Ov 2.5 - homolog of IL-10; Ov 4.5 - homolog of Bcl-2; Ov 5 - homolog of G-protein coupled receptor), in tissues of bison and cattle experimentally infected with OvHV-2. In four bison with primarily necrotizing lesions, we detected mRNA for ORF 25, Ov 4.5, and Ov 5. The presence of ORF 25 suggests that the lesions may be due to direct viral lysis and antiviral immune responses. In an infected steer in which the lesions were primarily lymphoproliferative, only mRNA for Ov 4.5 was consistently detected. These findings suggest that lymphoproliferative lesions are not associated with productive viral infection, and that the anti-apoptotic viral Bcl-2 mediates lymphoproliferation. In addition to providing new insights into the pathogenesis of MCF, these studies may also identify mRNA targets that distinguish animals with active infections from those with subclinical latent infections.